Preliminary data suggest that HPV 6, 11, 16, 18, 31, or 33 may be detected in genital tract specimens of at least 50% sexually active women, and in perhaps as much as 20% of sexually inexperienced girls. HPV 6 or 16 DNA has also been detected in samples of normal oral epithelium in 35% to 40% of adults and 10% of children. In addition, over 2/3 of sexually experienced women and 1/3 of sexually inexperienced women were found to have antibodies to HPV 6 L1 antigen. Implications of these data are the following: 1) presumed genital types of HPV are ubiquitous and commonly transmitted by non-sexual contact; 2) HPV genital infection is usually subclinical; 3) other factors influence the epithelial manifestation of HPV infection; and/or 4) evolving PCR and serologic methods are less than 100% specific. To address these questions, a prospective study of 500 randomly selected, sexually inexperienced, university freshman women, 17 to 19 years of age is proposed. Women will be followed over the course of their four year education with tri-annual examinations that include genital tract, oral and blood specimens for detection of presumed genital HPVs by PCR, Southern and dot blot, serologic assay, cytology, and colposcopy. At each visit, women will complete a standardized gynecologic history and clinical examination. Women who become sexually active (estimated to be 85%) will be asked to undergo an additional examination within one week of their sexual debut and women who report establishing a monogamous sexual relationship will be asked to have their male partner examined for evidence of HPV infection. Conceptually, this project is an extension of Project 1, which investigates risk of perinatal and childhood acquisition of HPV, and of Project 3 which will examine several aspects of the humoral immune response over time and relation to other measures of HPV infection. Information gained in Project 4 on the pathogenesis of HPV infection of human keratinocytes in the presence of chemical carcinogens or growth modulators will suggest strategies for the analysis and interpretation of data collected in Projects 1-3.